Gorskaya Yu F, Danilova T A, Nesterenko V G
Laboratory of Immunity Regulation, N. F. Gamaleya Institute of Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Russia.
Bull Exp Biol Med. 2011 Jun;151(2):210-4. doi: 10.1007/s10517-011-1291-2.
The study was carried out on CBA mice using the method of heterotopic transplantation. A fragment of the femoral bone marrow (1/2) or spleen (1/5 of the organ) was transplanted under the renal capsule of a recipient. The following donor-recipient cross-transplantation variants were studied: young-young (Y-Y), young-old (Y-O), old-old (O-O), and old-young (O-Y). Cell suspensions were prepared from 2-month transplants inoculated in monolayer cultures and the cloning efficiency (ECF-F) of stromal precursor cells (CFC-F) was evaluated. The bone marrow transplant ECF-F and the count of CFC-F in the O-O group were 8-fold lower than in the Y-Y group. In the O-Y group, ECF-F was 3-fold higher than in the O-O group, but by 2.5 times lower than in the Y-Y group. ECF-F in Y-O group was 2-fold lower than in Y-Y group. The ECF-F and CFC-F count in spleen transplants in the O-O group were 4- and 6-fold lower, respectively, than in Y-Y group. However, in O-Y group ECF-F was 7-fold higher than in O-O group and higher than even in Y-Y group. The weight of induced ectopic bone tissue after transplantation of the osteoinductor (fragments of the allogenic urinary bladder mucosa) was 2-fold lower in the O-O vs. Y-Y group. However, comparison of the ectopic bone tissue weights in different experimental groups showed that osteoinductor activity of the bladder epithelium did not decrease, but increased 3-fold with age (O-Y:Y-Y). A 5-fold reduction of this proportion in groups where the osteoinductor was transplanted from old donors to old and young recipients (O-Y:O-O) could be attributed to age-specific reduction of the count of inducible osteogenic precursor cells (IOPC). The data in general suggest that age-specific reduction of the stromal precursor count and functional activity could be caused by the true reduction (exhaustion) of cell pool (bone marrow CFC-F; presumably, IOPC) and by the regulatory effects of the organism (bone marrow and splenic CFC-F, IOPC). These data seem to be significant for understanding of the role of osteogenic stromal precursor cells in the development of age-associated bone tissue defects, for example, senile osteoporosis.
本研究采用异位移植法对CBA小鼠进行。将一段股骨骨髓（1/2）或脾脏（器官的1/5）移植到受体的肾被膜下。研究了以下供体-受体交叉移植变体：年轻-年轻（Y-Y）、年轻-年老（Y-O）、年老-年老（O-O）和年老-年轻（O-Y）。从接种于单层培养物中的2个月移植组织制备细胞悬液，并评估基质前体细胞（CFC-F）的克隆效率（ECF-F）。O-O组的骨髓移植ECF-F和CFC-F计数比Y-Y组低8倍。在O-Y组中，ECF-F比O-O组高3倍，但比Y-Y组低2.5倍。Y-O组的ECF-F比Y-Y组低2倍。O-O组脾脏移植的ECF-F和CFC-F计数分别比Y-Y组低4倍和6倍。然而，在O-Y组中，ECF-F比O-O组高7倍，甚至高于Y-Y组。在移植骨诱导剂（同种异体膀胱黏膜碎片）后，O-O组与Y-Y组相比，诱导异位骨组织的重量低2倍。然而，不同实验组异位骨组织重量的比较表明，膀胱上皮的骨诱导剂活性并未降低，而是随年龄增长增加了3倍（O-Y:Y-Y）。在骨诱导剂从年老供体移植到年老和年轻受体的组中（O-Y:O-O），这一比例降低了5倍，这可能归因于可诱导成骨前体细胞（IOPC）数量的年龄特异性减少。总体数据表明，基质前体细胞数量和功能活性的年龄特异性减少可能是由于细胞池（骨髓CFC-F；可能还有IOPC）的真正减少（耗尽）以及机体的调节作用（骨髓和脾脏CFC-F、IOPC）。这些数据对于理解成骨基质前体细胞在与年龄相关的骨组织缺陷（如老年性骨质疏松症）发展中的作用似乎具有重要意义。
